Fittingly, he stole the show as Barcelona hit Real Sociedad for six, scoring twice and creating another to mark the occasion in serious style.
The Argentine's roll of honour in that time is far too long to list in full, but the headlines from his 768 games so far include some staggering numbers: 663 goals (more than anyone has ever scored for a single club in football history), 291 assists, 48 hat-tricks and 33 major trophies.
Those are figures which place him firmly in the debate for the greatest player of all time, yet even they do not fully illustrate the influence Messi has had on almost every Barcelona game he has played in since his debut 17 years ago.
Regardless of where you stand on the GOAT debate, there is little argument that Messi is the sole contender for the title of Barca's greatest ever - no mean feat at a club which boasts the likes of Johan Cruyff, Diego Maradona, Ronaldo, Ronaldinho, Xavi and Andres Iniesta among their alumni.
Speculation over the 33-year-old's future continues to rage with his contract expiring this summer and having been kept at the club against his will last year, and there remains a very real possibility that his sparkling Camp Nou career could be coming to an end sooner rather than later.
Even if that does happen, Messi has already left behind a generation of genius, almost two decades of consistently hair-raising, goosebump-inducing and jaw-dropping moments as a Barcelona player, and his record-breaking appearance is as good a time as any to delve into that treasure trove of artistry.
With that in mind, Sports Mole has taken on the thoroughly enjoyable task of picking out Messi's 20 greatest ever Barcelona performances - try as we might, we could not cut the list down any more, and we are still omitting some displays which would be career-defining matches for most players.
Sit back and enjoy the very best of the best!
20. Barcelona 2-0 Manchester United (May 27, 2009)
It is a mark of the ludicrous standard in this list that a superb performance in a Champions League final only makes it to number 20.
The buildup to the 2009 Champions League final was all about Messi vs. Cristiano Ronaldo - a rivalry which was still in its early stages but which had already generated significant hype even before the latter's move to Real Madrid.
Ronaldo already had one Ballon d'Or under his belt heading into the Rome showdown but Messi was on course to usurp his great rival as the world's best player, and his performance at the Stadio Olimpico went a long way towards sealing his first of six.
Despite pre-match talk of Ronaldo's aerial ability being a major advantage he had over Messi, it was the Argentine who used his head to greater effect as Pep Guardiola's side clinched Champions League glory.
A one-booted Messi produced a gravity-defying leap to send a looping header over Edwin van der Sar and into the back of the net, sealing a third Champions League title for his club and capping another fine individual performance on the biggest stage.
19. Barcelona 4-0 Bayern Munich (April 8, 2009)
Barcelona suffered Champions League humiliation at the hands of Bayern Munich last year, but in 2009 it was their turn to inflict punishment on the German giants as they effectively booked their place in the semi-finals with a game to spare.
Messi opened the scoring after only nine minutes by rolling the ball into the bottom corner, and added an assist just three minutes later with a reverse pass through for Samuel Eto'o to finish.
The Argentine netted his second of the game and Barcelona's third in the 38th minute, diving in to bravely prod home from close range.
Messi was also heavily involved in the buildup for the fourth goal as Barcelona put the game beyond the Bavarians before half time of the first leg, remaining on course for the Champions League glory they achieved that year.
18. Barcelona 5-0 Eibar (February 22, 2020)
The most recent entry on this list, Messi's seventh four-goal haul of his career came in a 5-0 rout of Eibar in February of last year.
Messi's first was the pick of the bunch as he skipped past three defenders before applying a brilliant finish, but his second and fourth goals were also fine solo efforts in their own right.
The Argentine had the run of the place as he burst past two more defenders and slotted home for his second, clipped a loose ball home for his hat-trick having tried to set up Antoine Griezmann and then toyed with the Eibar goalkeeper for his fourth goal.
By this stage of his career the supporting cast that had played such a big role in many of the other inclusions on this list had largely broken up, but this game was a firm reminder - if one was needed - that Messi continues to set other-worldly levels regardless of who is around him.
17. Barcelona 5-0 Atletico Madrid (September 24, 2011)
Messi has a million ways to make goalkeepers look silly, and one of his favourites is to beat them at their near post - just as he did to Thibaut Courtois for his brilliant opening goal in this rout of Atletico Madrid early in the 2011-12 season.
That goal made it 3-0 after just 26 minutes, with Messi having already forced an own goal to chalk up an assist, and he went on to add two more goals in the second half for yet another hat-trick.
The number 10's second goal was arguably even better as he pounced on a loose ball before coasting past a couple of defenders and firing home through the legs of a third, and there was another nutmeg to complete the hat-trick as he beat Courtois from a tight angle again.
The performance came just a week after scoring a hat-trick and claiming two assists against Osasuna, offering early glimpses of what was to come in a season which saw him score an unprecedented 50 goals in the league alone.
16. Barcelona 5-2 Getafe (April 18, 2007)
Picking out Lionel Messi's greatest ever goal is a whole different rabbit hole of footballing splendour to go down but, despite there being so many to choose from, you will be hard-pressed to find one better than his solo effort against Getafe in 2007.
Messi had already begun to build his reputation as Diego Maradona's long-awaited worthy heir by this stage, and the comparisons between the diminutive duo only grew when Messi produced a piece of genius eerily reminiscent of Maradona's 'Goal of the Century' against England at the 1986 World Cup.
Indeed, the strike was voted as Barcelona's greatest ever goal - just one of the countless indelible marks Messi has made on the club.
While such a moment unsurprisingly stole the headlines as the standout feature of the match, Messi also set up the opening goal for Xavi and lashed home the third - all within the first half.
The Argentine's magic appeared to be enough to send Barca into the Copa del Rey final, but without Messi in the squad they contrived to lose the second leg of the semi-final 4-0 as Getafe pulled off a stunning comeback.
15. Barcelona 4-0 Manchester City (October 19, 2016)
Having wreaked such havoc as a Barcelona player under Guardiola, Messi came back to haunt his former manager in the way only he can during this Champions League group game in 2016.
The striker took advantage of some statuesque Man City defending to open the scoring after 17 minutes, but it was in the final half an hour of the game - after Man City had been reduced to 10 men - where he really took matters into his own hands.
Barca would not be denied their fourth, though, with Messi teeing up Neymar again just two minutes later and the Brazilian this time making no mistake as their reunion with their most successful ever boss ended in a 4-0 triumph.
14. Real Madrid 2-6 Barcelona (May 2, 2009)
Pointing out that playing a starring role in a six-goal showing away to Real Madrid was one of the standout performances of Messi's career may be stating the obvious, but the importance of this particular game goes even further than the fact that Barcelona recorded their biggest ever win at the Bernabeu.
Deployed as a 'false nine' for the first time by Guardiola, Messi assisted Barcelona's first goal for Thierry Henry to level the scores after 18 minutes and then went on to add two more of his own.
The first was a poked finish 10 minutes before half time, while his second saw him toy with Casillas before beating him at the near post to make it 5-2.
Messi will feel that he could and should have had more too, missing three very presentable chances and coming close with an audacious lob in addition to his two goals and one assist.
Even so, he had once again made the Bernabeu his playground as Barcelona enjoyed arguably the standout moment of an incredible season in which they became the first Spanish club to win the treble.
13. Barcelona 4-0 Espanyol (May 5, 2012)
Always the man for a big occasion, Messi ensured that Guardiola's final home game in charge of the club - a derby against local rivals Espanyol, no less - was marked in suitable style.
It came at the end of a season in which Messi in particular reached new heights, and it was his opening goal of the contest - a pinpoint 30-yard free kick - which was the pick of his four on the night.
The Argentine rippled the side-netting with another before adding a hat-trick in the final 30 minutes - two from the penalty spot, including one he won himself, and a brilliant effort to secure the matchball sandwiched between those spot kicks.
It was one of seven four-goal hauls in Messi's career and his third of the Guardiola era, bidding farewell to the man who got the most out of him in fine fashion.
12. Levante 0-5 Barcelona (December 16, 2018)
As far as decisive influence on a single game is concerned, this might just be top of the pile throughout all 768 of Messi's Barcelona appearances.
The Argentine scored three and created two more to single-handedly tear Levante apart, directly contributing to all five goals in a 5-0 hammering and setting the tone with his impossible opening assist for Luis Suarez 10 minutes before half time.
A 17-minute hat-trick either side of the interval then followed, with Messi tucking the first under the keeper with his right foot, sweeping a second into the bottom corner from the edge of the box and then firing home a third from close range on the hour mark.
The maestro was not done there, though, ending the match as he started it with a pass into the path of the marauding Gerard Pique, who capped off the rout.
11. Barcelona 3-1 Manchester United (May 28, 2011)
Two years on from facing off in a Rome Champions League final, Barcelona and Manchester United renewed acquaintances in the showpiece event at Wembley and once again it was the Spanish outfit who were celebrating at the end of it.
Widely regarded as the peak of Guardiola's Barca - and many would argue the best club football ever seen - Messi, Xavi, Iniesta and co utterly outclassed a United side that had reached the final three times in four years.
Sir Alex Ferguson, Rio Ferdinand and Nemanja Vidic were among the Man United men to hail that Barcelona team as the best they had ever faced in the wake of the game, with Messi shining brightest in a man-of-the-match performance.
The forward's passionate celebration after his goal - a lethal low drive into the bottom corner from range - spoke volumes about how much the match meant to him, and he also played a big part in his side's third to wrap up the triumph.
10. Barcelona 8-0 Osasuna (September 17, 2011)
Messi has scored three goals and assisted two more in the same game on three separate occasions, and it is a mark of his quality that not all of those performances - which would be career-crowning achievements for any other player - even make it onto this list.
His star showing in an 8-0 obliteration of Osasuna does make the cut, though, and his haul could have been even more impressive, having also hit the inside of the post with a header and struck the crossbar with an audacious lob.
Barca ran riot throughout, racing into a 5-0 lead within 41 minutes with Messi having a direct hand in three of those goals - scoring twice himself and setting up Cesc Fabregas for another.
It was a similar story in the second half as Messi chipped the ball through for Xavi to score a superb lob, and the Argentine fittingly put the icing on the cake himself with a trademark strike to cap off the scoring and complete his hat-trick.
9. Barcelona 3-2 Real Madrid (August 17, 2011)
The Spanish Super Cup may not be the most prized trophy in Messi's considerable collection, but any victory at Real Madrid's expense means that bit more and the 2011 Super Cup in particular will go down as a memorable moment in his career.
Messi had already had a decisive say in the first leg at the Bernabeu, scoring once and creating another in a 2-2 draw, but he went one better in the return fixture at Camp Nou.
The Argentine played the ball through for Iniesta to open the scoring, before squeezing home an impudent finish with his right foot to restore Barca's lead just before half time.
Karim Benzema then appeared to have forced extra time with an equaliser, only for Messi to have the last laugh once again as his 88th-minute first-time volley sealed the trophy for the Catalans - one of five pieces of silverware Guardiola's all-conquering side won that calendar year.
8. Barcelona 3-0 Liverpool (May 1, 2019)
Just like goal number 500, goal number 600 came in sensational style as he seemingly put Barcelona on course for another Champions League final at the expense of Liverpool in 2019.
Messi's first of the semi-final first leg was one of the easier goals of his career as he ran a loose ball into an empty net after Luis Suarez had hit the crossbar, but his second seven minutes later was anything but straightforward.
Even for a player of Messi's quality, the free kick Barcelona were awarded in the 82nd minute appeared to be too far out to go for goal, but the Argentine lined it up nonetheless.
Messi could make a strong claim to be regarded as the best free-kick taker in history too, and this effort was arguably his best, leaving Alisson Becker no chance with a perfectly-placed stunner from 35 yards.
That made it 3-0 on the night and appeared to all-but secure Barcelona's place in the final, only for Liverpool to launch one of the greatest Champions League comebacks of all time in the second leg at Anfield.
7. Barcelona 4-1 Arsenal (April 6, 2010)
Arsenal have been on the wrong end of many a Messi masterclass, and four of his nine goals against the Gunners came on one mesmerising night in April 2010.
Arsene Wenger's side had taken the lead at Camp Nou before Messi took the game by the scruff of its neck, setting the tone by blasting his first into the top corner from the edge of the box.
The second saw him produce a cool-headed finish with his right, while he brought up the hat-trick before half time with a trademark chip which he made look outrageously easy.
Having led the Arsenal defence a merry dance and almost single-handedly booked Barcelona's place in the quarter-finals following a 2-2 draw in the first leg, Messi then capped off the scoring with a drilled finish to record the first four-goal haul of his career.
6. Real Madrid 3-4 Barcelona (March 23, 2014)
A Clasico that had it all: seven goals, a Sergio Ramos red card, three penalties and, of course, a Messi hat-trick - his second three-goal, one-assist haul in a row in La Liga.
The assist came for the opening goal of the contest after only seven minutes as he threaded the ball through for Iniesta to score, but a quickfire Karim Benzema brace turned the game around until Messi got his own name on the scoresheet for the first time shortly before half time.
Madrid took the lead again through Ronaldo's penalty 10 minutes after the interval, but Messi then outshone his eternal rival with two penalties of his own - the second placed perfectly into the top corner.
It was the second Clasico hat-trick of Messi's career, and his only one at the Bernabeu, and also goes down as his best return in a Clasico after he had a direct hand in all four of his side's goals.
5. Barcelona 7-1 Bayer Leverkusen (March 7, 2012)
In terms of returns in a single game, this Champions League last 16 second leg against Bayer Leverkusen stands alone as the best of Messi's incredible career.
The Argentine became the first player to ever score five goals in a single Champions League match, while it is also the only time Messi himself has achieved that feat in a game across all competitions.
He had already scored one and created another in the first leg to put Barca in charge of the tie, but his five-star showing against Leverkusen took what would become a record-breaking year to new heights.
Messi's five goals consisted of two outrageous lobs, two pinpoint curlers into the bottom corner and an opportunistic finish from a tight angle, sealing a 10-2 aggregate triumph.
Barca would ultimately fall short in that season's Champions League, but Messi ended 2011-12 with a ridiculous 73 goals in 60 games, becoming the club's all-time leading scorer at the age of just 24 along the way.
4. Barcelona 3-3 Real Madrid (March 10, 2007)
A defining feature of Messi's career has been producing the goods in the biggest games, as this list showcases, and perhaps the first major glimpse of that came when the then 19-year-old announced himself on the Clasico scene.
The Argentine has gone on to score more goals against Real Madrid than any other player, and the first three of those all came in this match as Messi recorded his first career hat-trick in style.
Madrid took the lead three times at Camp Nou, and on each occasion Messi hit back. The first was a trademark finish into the bottom corner and the second an opportunistic finish into the roof of the net, but he saved the best until last.
The forward took matters into his own hands by dancing away from three Madrid players and firing the ball into the bottom corner in the 91st minute, rescuing a point which, at the time, appeared to be crucial in the La Liga title race.
Ultimately his heroics would be in vain, with Madrid and Barca finishing level on points at the top of the table but Madrid winning the title by virtue of their superior head-to-head record.
3. Real Madrid 0-2 Barcelona (April 27, 2011)
There has never been a Champions League final Clasico before, and the closest we have got came when the two famous rivals faced off in the 2010-11 semi-finals.
In a notoriously ill-tempered history, this was arguably the peak of the Clasico rivalry, with Jose Mourinho in charge of Real Madrid and Guardiola setting new standards as Barcelona boss.
This semi-final first leg had already been littered with incident before Messi stunned the Bernabeu again, with a Barcelona sub seeing red before Pepe was sent off for the hosts.
It was Messi's brilliance which ultimately made the difference, though; the forward darted across his man at the near post to score the opener after 77 minutes, before producing one of the great Champions League semi-final goals to wrap up the contest.
With just three minutes of normal time remaining, Messi collected the ball 40 yards from goal before turning on the gas to leave four Real Madrid defenders in his wake and sliding the ball past Iker Casillas.
2. Real Madrid 2-3 Barcelona (April 23, 2017)
There could have been no more fitting way for Messi to bring up his 500th Barcelona goal than a stoppage-time winner in a Clasico against Real Madrid at the Bernabeu.
The six-time Ballon d'Or winner celebrated his milestone goal in iconic fashion, raising his shirt up in front of a begrudgingly bedazzled Bernabeu crowd having once again haunted his club's greatest rivals.
It capped an eventful game for Messi, who had earlier been left bloodied and bruised by a Marcelo elbow to the face, and was also on the end of a two-footed Sergio Ramos challenge which saw the Madrid stalwart sent off.
As is so often the case, Messi's headline-grabbing heroics were not his solitary contribution to the game either, having already scored a superb individual effort to level the scores in the first half.
At the time, the win appeared to have kept Barcelona's title hopes alive, although they went on to finish three points adrift of their great rivals.
1. Barcelona 3-0 Bayern Munich (May 6, 2015)
Messi's career is littered with unforgettable moments which leave onlookers with no option but to simply sit back and admire, and one of the most notable of those was his second goal in the 2014-15 Champions League semi-final first leg against Bayern Munich.
The forward skipped past Jerome Boateng with embarrassing ease, leaving the beaten defender on the floor in his wake, before making a mockery of one of the greatest goalkeepers in history by lifting the ball over Manuel Neuer with his 'weaker' right foot.
That iconic solo goal would have been good enough in isolation, but it was just one of the decisive impacts made by Messi during a virtuoso 25-minute period which saw him score twice and assist another.
The Argentine fired a powerful low strike past Neuer at his near post in the 77th minute, produced his standout moment of magic just three minutes after that and then sent Neymar through to cap off the scoring four minutes into added time.
Barcelona went on to lose the second leg 3-2 in Germany, but progressed to the final on aggregate and then beat Juventus to win the trophy.